Hereditary chromosome diseases which show predisposition to cancer may be explained by genetic defects in the cell's repair and detoxification capacity towards damages to DNA. Our studies have and will concentrate on three related approaches. 1. To analyze possible deficiencies in naturally occurring human mutant cells from ataxia telangiectasia activities of enzymes which may be involved in DNA repair. These include ligase, N-glycosylase, apurinic and apyrimidinic endonuclease, gamma endonuclease, superoxide dismutase and catalase activities in crude cell extracts. 2. To isolate repair-replication mutants with a model cell system with which to study specific defect in DNA repairs. The cell system used is from Chinese hamster ovary (CHO) and both UV and gamma sensitive and resistance will be examined along with mitomycin C, psoralen-UVB and caffeine which directly or indirectly cause damage in DNA. 3. To study specific genes for their organization and expression and factors which can alter tham. The genes to be studied are (a) the histones, the basic chromosomal proteins and (b) metallothionein, a protein, the function of which may lie in the sequestering of toxic metals like cadmium. Cadmium causes chromosome breakage and may also interfere with enzyme fidelity.